Halinchondrin analogs have been disclosed as having anti-cancer and antimitotic activity (U.S. Pat. No. 6,214,865, incorporated herein by reference). In particular, Halichondrin B has been reported as a potent anticancer agent that was first isolated from the marine sponge Halichondria okadai (U.S. Pat. No. 6,214,865; WO 2005/118565 A1 and WO 2009/124237 A1, all incorporated herein by reference).

(3R)-2,4-diiodo-3-methylbut-1-ene (7a) has been disclosed as a building block in the synthesis of halichondrin natural products and derivatives ((1)(a) Katrina, L. et al., Angewandte Chemie, International Edition, 2009, v. 48, no. 13, 2346-2350, (b) Kim, D-S. et al., Journal of the American Chemical Society, 2009, v. 131, no. 43, 15636-15641, (c) Guo, H. et al., Journal of the American Chemical Society, 2009, v. 131, no. 42, 15387-15393, (d) Choi, H-w. et al. Organic Letters, 2002, v. 4, no. 25, 4435-4438, all incorporated herein by reference). The preparation of (3R)-2,4-diiodo-3-methylbut-1-ene (7a) has been disclosed by two synthetic methods,1b both of which can be unsuitable for large scale manufacturing of pharmaceutical quality material. The first approach involves the asymmetric SN2′ reaction of a cuprate. In addition to the difficulties that can be inherent to cuprate chemistry, the product is isolated in 98% enantiomeric excess (e.e.), with its enantiomer present in levels well above the 0.10% that can generally be required by regulatory agencies. The second method involves the use of trimethylaluminum, a pyrophoric chemical, which can pose a significant hazard for large scale reaction.

There is a need in the art for a process for preparation of (3R)-2,4-diiodo-3-methylbut-1-ene (7a), and its analogs (7), that can be used in the preparation of halichondrin natural products, its derivatives and analogs, such as, for example and without limitation, eribulin the compounds described in recent publication of S. Narayan and others (Bioorganic and Medicinal Chemistry letters, 2011, 1630-1633; Bioorganic and Medicinal Chemistry letters, 2011, 1634-1638, Bioorganic and Medicinal Chemistry letters, 2011, 1639-1643), and other eribulin analogs with modified side chains on position C32 of eribulin. In addition, there is a need in the art for a process for preparation of (3R)-2,4-diiodo-3-methylbut-1-ene (7a), and its analogs (7), that can be prepared from commercially available starting material. Moreover, there is a need in the art for a process for the preparation of (3R)-2,4-diiodo-3-methylbut-1-ene (7a), and its analogs (7), that lead to (3R)-2,4-diiodo-3-methylbut-1-ene (7a), and its analogs (7), in high enantiomeric excess. In addition, there is a need in the art for a process for preparation of (3R)-2,4-diiodo-3-methylbut-1-ene (7a), and its analogs (7), where the process is scalable.